One Patient Profile Emerges as Extra-Well Suited for Extra-Long DAPT After PCI

There was strong evidence for extending dual antiplatelet therapy (DAPT) beyond the standard 12 months in selected patients with multivessel coronary artery disease (CAD), the DAPT-MVD trial found.

These were nonelderly patients who’d undergone coronary stenting, for an acute coronary syndrome (ACS) in virtually all cases, and were finishing a 12-month course of DAPT without having experienced major ischemic or bleeding complications, demonstrating low bleeding risk.

In these patients, having DAPT extended another 12 months (followed by aspirin thereafter) resulted in a lower incidence of death from cardiovascular causes, nonfatal myocardial infarction, and nonfatal stroke at 36 months compared with aspirin monotherapy (5.8% vs 6.8%, HR 0.82, 95% CI 0.69-0.98), according to Bo Yu, MD, of Second Affiliated Hospital of Harbin Medical University in China, and colleagues.

In addition, rates of clinically relevant or major bleeding indicated no safety issues with extended DAPT over aspirin alone (1.4% vs 1.5%, HR 0.89, 95% CI 0.61-1.30), study authors reported in the New England Journal of Medicine.

“Our results suggest that for patients with multivessel disease who present with an ACS, a standard 12-month duration of DAPT may be insufficient, even in those without ischemic or bleeding events up to that point. These results are concordant with those of previous trials that showed the value of extended antiplatelet therapy in high-risk secondary prevention cohorts,” Yu and colleagues wrote.

DAPT with aspirin and oral P2Y12 inhibitors is the cornerstone therapy for preventing thrombotic complications after percutaneous coronary intervention (PCI), the cost being an increased risk of bleeding. In the ACS population, the standard antithrombotic regimen is 12 months of DAPT after stenting to reduce the risk of ischemic events; in those with no high risk of bleeding, guidelines from 2021 say it is reasonable to extend DAPT beyond 1 year.

With the present report, the DAPT-MVD investigators were able to isolate a unique population with high ischemic risk but low bleeding risk, a “decoupling of ischemic benefit from hemorrhagic harm,” according to Kyung Woo Park, MD, and Jeehoon Kang, MD, both of Seoul National University Hospital.

The first step was to draw from the pool of people with multivessel CAD, for whom the risk of ischemic events remains high due to stented segments, vulnerable plaques, and progression of other untreated plaque, the duo explained in an accompanying editorial.

“By strictly selecting patients younger than 75 years of age, who had already received a full year of DAPT without adverse events, they successfully identified a cohort that could reap the atherothrombotic benefits of prolonged P2Y12 inhibition without paying the price of hemorrhage,” Park and Kang noted.

“The reduction in the risk of myocardial infarction observed with extended DAPT was driven primarily by fewer events arising from nontarget vessels rather than from the stented lesions, a finding that suggests that prolonged P2Y12 inhibition may stabilize untreated vulnerable plaques,” the editorialists added.

DAPT-MVD was an open-label trial conducted at nearly 100 Chinese centers from 2020 to 2024.

Participants were 8,250 nonelderly patients age 18 to 75 with multivessel CAD who’d undergone PCI and developed no major ischemic or bleeding complications while on 1 year of DAPT. Multivessel disease was defined as two or more major epicardial coronary arteries with a diameter stenosis of at least 50%, with up to 30% diameter stenosis in the left main coronary artery.

Patients were randomized receive an additional 12 months of DAPT (daily clopidogrel 75 mg and aspirin 75-150 mg) or aspirin monotherapy (75-150 mg daily).

Baseline characteristics were similar between groups. The overall mean age was 61 years, and 30.3% were women. About 28% had diabetes. Virtually all patients (98.3%) presented to index PCI with ACS (34.0% a myocardial infarction). PCI with drug-eluting stent implantation was performed on a single vessel in 79.5% of cases and on multiple vessels in 20.5%.

Average time from index PCI to randomization was 378.6 days. All participants had been on DAPT, namely clopidogrel/aspirin (67.1%) or ticagrelor/aspirin (32.9%).

Follow-up reached a median 34.3 months in the trial.

There were no significant differences in any individual components of the primary efficacy composite outcome between extended DAPT and aspirin monotherapy cohorts, with the potential exception of nonfatal myocardial infarction.

DAPT-MVD did leave room for potential bias through the study’s open-label design, Yu’s group acknowledged.

Additionally, the study findings may not be applicable to other DAPT regimens and populations. Patients with planned use of anticoagulants or contraindications to platelet P2Y12 inhibitors during the trial period were excluded from the trial.

“The patients that were evaluated in the DAPT-MVD trial were exclusively Chinese, a population with a known high prevalence of CYP2C19 loss-of-function alleles, which reduce clopidogrel bioactivation, and a low prevalence of obesity,” added Park and Kang.

“It should also be noted that even with extended DAPT, 5.8% of these patients in clinically stable condition still had a major ischemic event, a finding that reminds us that the residual risk from widespread coronary atherosclerosis cannot be completely eliminated with platelet inhibition,” they stressed. “Future progress will depend not only on longer platelet inhibition but also on new strategies that target the underlying atherosclerosis.”